Title

Rapid Induction of Dendritic Spine Morphogenesis by trans-Synaptic EphrinB-EphB Receptor Activation of the Rho-GEF Kalirin

Document Type

Article

Abstract

The morphogenesis of dendritic spines, the major sites of excitatory synaptic transmission in the brain, is important in synaptic development and plasticity. We have identified an ephrinB-EphB receptor trans-synaptic signaling pathway which regulates the morphogenesis and maturation of dendritic spines in hippocampal neurons. Activation of the EphB receptor induces translocation of the Rho-GEF kalirin to synapses and activation of Rac1 and its effector PAK. Overexpression of dominant-negative EphB receptor, catalytically inactive kalirin, or dominant-negative Rac1, or inhibition of PAK eliminates ephrin-induced spine development. This novel signal transduction pathway may be critical for the regulation of the actin cytoskeleton controlling spine morphogenesis during development and plasticity.

Keywords

Blotting; Western; Carrier proteins; Cells; Cultured; Cellular signal transduction; Dendrites; Dendrites/drug effects; Dendrites/ultrastructure; Fixation (Histology); G proteins; Guanine Nucleotide Exchange Factors/physiology; Hippocampus (Brain); Hippocampus/cytology; Hippocampus/embryology; Humans; Indicators and Reagents; Men; Morphogenesis; Neuroplasticity; Neuronal Plasticity/physiology; Phosphorylation; Receptors; Eph Family/physiology; Rho Guanine Nucleotide Exchange Factors; Signal Transduction/physiology; Synapses; Synapses/physiology; Synapses/ultrastructure; Tissue Fixation; Transfection; Western immunoblotting; Women; rac1 GTP-Binding Protein/physiology

Disciplines

Life Sciences | Medical Sciences | Neurosciences

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